Alkylated benzyl, nu-decyl, dimethylammonium hydroxide and salts thereof



ALKYLATED BENZYL, N-DECYL, DIMETHYLAM- MONIUM HYDROXIDE AND SALTS THEREOF Giuliana C. Tesoro, Dobbs Ferry, N. Y., and Reginald L. Wakeman, Conshohocken, Pa., assignors to Onyx Oil and Chemical Company, Jersey City, N. J., a corporation of New Jersey No Drawing. Application November 3, 1953,

Serial No. 390,094

The terminal portion of the term of the patent commencing April 27,1971 has been disclaimed.

3 Claims. (Cl. 260567.6)

This invention relates to antimicrobial substances and specifically to quaternary ammonium compounds that show; high antimicrobial activity. The present application 1s in part a continuation of copending application Serial No. 144,378, filed February 15, 1950, now U. S. Patent No. 2,676,986.

The antimicrobial activity of quaternary ammonium compounds has been known for some time as is evidenced by U. S. Patent No. 2,108,765, granted February 15, 1938, to Domagk. These compounds have come into fairly wide use as antiseptic agents, but unfortunately, commercially available compounds do not exhibit a activity as high as is known to be obtainable. 1

Thus Lawrence et al. have reported in an article in the Journal of the American Pharmaceutical Association, volume 36, No. 51, pages 353 to 358 (November 1947), the phenol coefficients of several (alkyl, benzyl, dimethyl) ammonium chlorides as follows:

Phenol coefiicient of alkyl dimethyl benzyl ammonium chlorides Sal monella Staphylococcus typhosa G'ILTEILS Alkyl Group Less than 16 Less than 16 50 55 Among the objects of the present invention is the provision of improved commercially attractive quaternary ammonium compounds having higher antimicrobial activity than anything indicated by Lawrence et al.

A further object of the present invention is the provision of new antimicrobial quarternary ammonium compounds having only one long carbon chain with ten carbon atoms.

The above, as well as additional objects of the present invention, will be more readily understood from the following description of exemplifications thereof.

It has been discovered that outstanding antimicrobial activities can be readily provided in commercially feasible quaternary benzyl, decyl, dimethyl, ammonium compounds in which the benzene ring of the benzyl group is alkylated with an alkyl group having from four to five carbon atoms. Examples of these compounds are:

1. {Ar-n-butyl-benzyl, decyl, dimethyl) ammonium chlo- 2. (Ar-n-amyl-benzyl, decyl, dimethyl) ammonium chloride 3. (Ar-secondary-butyl, benzyl, decyl, dimethyl) ammonium chloride 4. (Ar-tertiary-butyl, benzyl, decyl, dimethyl) ammonium chloride 5. (Ar-isoamyl-butyl, benzyl, decyl, dimethyl) ammonium chloride 6. (Ar-secondary amyl-butyl, benzyl, decyl, dimethyl) ammonium chloride The above compounds appear to be equally etfective where they are in the form of pure isomers or mixtures 2,700,684 l aten ted J an, 25,

ice

of isomers in which the alkyl group on the benzene ring occupies various positions such as those they take upon chloromethylation of the corresponding alkyl benzene. The resulting alkyl-group-containing benzyl chloride can be used as a starting material to make the above compounds.

Aspecifie example of the proportion of one of'the compounds of the present invention is as follows:

(Ar-n-butyl benzyl, decyl, dimethyl) ammonium chloride Forty-five grams (0.25 mol) of Ar-n-butyl-benzyl chloride (an isomeric mixture prepared by chloromethylating n-butyl-benzene) and 47 grams (0.25 mol) of decyl di methyl amine were mixed and heated with mechanical stirring until the reaction became exothermic. The temperature was then maintained at to C. for thirty minutes or until the mixture became too stiff to stir. One hundred twenty-five'grams of cold water were then added, and the mixture was heated with stirring at 100 C. until the clear solution formed reached the calculated ionizable chloride content (4.05 per cent Cl for a 42.5 per cent solution indicating 100 per cent reaction). Thirty-three grams of water were then distilled off to remove unreacted organic material and to give a clear, pale yellow 50 per cent solution containing 4.75 per cent chloride.

The other compounds are prepared in the same manner using the appropriately alkylated benzyl chloride. Readily available mixtures of isomeric alkyl benzyl compounds or pure ortho, meta, or para alkyl benzyl chlorides can be used.

Compounds of the present invention can be prepared by processes other than that described above. One such alternative technique is to mix at a temperature of about 100 C. decyl bromide or chloride with a suitable Aralkylated benzyl dimethyl amine.

The activity of the above compounds appears to be associated exclusively with the cation portion of the molecule. These cations show substantially the same activity whether combined in the form of chlorides, bromides, other halides, or with the anions of other acids, including mineral acids such as nitric acid, sulphuric acid, orthophosphoric, metaphosphoric, pyrophosphoric, phosphorous acid, or any of the acids mentioned in the Domagk Patent No. 2,108,765, including the organic acids ethyl sulfuric acid, formic acid, acetic acid, lactic acid, tartaric acid, citric acid, benzene sulfonic acid, p-toluene sulfonic acid, benzoic acid, and salicylic acid. In fact, any salt of the cation with a water-soluble anion is suitable although for pharmaceutical use salts made with anions of non-toxic water soluble acids are preferred. In addition, the free quaternary ammonium hydroxide itself shows about the same activity. The free hydroxides are relatively strong bases readily prepared by reacting the corresponding halides with silver oxide, or the corresponding sulphate with an aqueous solution of barium hydroxide. The free base can be neutralized with any acid to form the desired antimicrobial compounds as listed above.

The Ar-butyland Ar-amyl-compounds of the present invention can also have the benzene rings chlorinated with one or two chlorine atoms, as by chloromethylating the corresponding Ar-chloro-butyl-benzene or Ar-chloroamyl-benzene. Such chlorinated compounds show an even higher activity.

It is extremely difiicult to isolate the prepared compounds in pure form inasmuch as they are unusually deliquescent and rapidly absorb water from the atmosphere and even from mixtures with absolute (over 96 per cent) ethanol. In high concentrations, that is, with only a small water content, the compounds of the invention do not lose water to anhydrous calcium chloride in a vacuum desiccator. The boiling down of concentrated aqueous solutions of these materials is not feasible by reason of the fact that even heating is impossible and the solutions tend to bump or suddenly liberate vapors with considerable violence, usually causing liquid to be shot out with the vapors. The quaternizing reactions do not go to completion in the absence of solvent because of mechanical difiiculties.

High concentrations (90 per cent or over) of the new quaternary compounds can be prepared by carrying out the solvent.

softness, for example,

tionally high the quaternizing in relatively absolute alcohol or acetone,

volatile solvents such as and then evaporating off Such 90 per cent preparations are clear, pale yellow, extremely viscous syrups which tend to form skins on their surface upon standing in a desiccator. The syrups are extremely soluble in water, ethanol, isopropanol, acetone, benzene, ethyl ether and ethyl acetate, although practically insoluble in petroleum ether. With dilute aqueous solutions of sodium picrate they react to form water-insoluble yellow oils. 7

he 90 per cent by weight (Ar-n-butyl benzyl, decyl, dimethyl) ammonium-chloride (the balance being essentially water) has a specific gravity of 0.928 at 30 C. with respect to water at the same temperature. Its index of refraction for the yellow sodium lines at 25 C. is 1.487. The syrups of the other compounds have corresponding values.

The new compounds can be prepared in dry form on a suitable carrier, such as urea, to yield free-flowing powders containing at least 20 per cent of the quaternary compound by weight.

By reason of the cationic surface nary compounds of the invention, effective as wetting, dispersing, They may be utilized as textile activity of the quaterthey are also highly or froth flotation agents. finishing agents to impart to the treated goods. Applied to woolen fabrics, they also exhibit valuable moth-proofing characteristics. They are not irritating to the skin or body nor toxic in use dilutions.

The characteristics of the new compounds include strong algicidal and fungicidal behavior as well as effective action as deodorants.

The compounds of the present invention show excepbactericidal activities as compared to the maximum value reported by Lawrence et al. This is indicated by the following phenol coetficients determined at 20 C. by the standard method given in the U. S.' Department of Agriculture Circular 198:

Staphylococ- Salmonella cus aureus typhosu,

1. (Ar-n-butyl benzyl) decyl dimethyl am- 'monium chloride 1, 000 690 2. (Ar-isoamyl benzyl) decyl dimethyl ammonium chloride l, 166 875 The other compounds of the present invention are of comparable activity.

As many apparently widely different embodiments of this invention may be made without departing from the spirit and scope hereof, it is to be understood that the invention is not limited to the specific embodiments hereof except as defined in the appended claims.

What is claimed is:

l. A quarternary ammonium compound selected from the class consisting of the free base and the salts with non-toxic water-soluble acids, of (Ar-alkylated benzyl, n-decyl, dimethyl) ammonium hydroxide in which the benzene ring is alkylated with an alkyl group having from four to five carbon atoms.

2. An (Ar-butyl benzyl, n-decyl, dimethyl) ammonium halide. 1 h An (Ar-amyl benzyl, n-decyl, dimethyl) ammonium 2,676,986 Wakeman et a1. Apr. 27, 1954 

1. A QUARTENARY AMMONIUM COMPOUND SELECTED FROM THE CLASS CONSISTING OF THE FREE BASE AND THE SALTS WITH NON-TOXIC WATER-SOLUBLE ACIDS, OF (AR-ALKYLATED BENZYL, N-DECYL, DIMETHYL) AMMONIUM HYDROXIDE IN WHICH THE BENZENE RING IS ALKYLATED WITH AN ALKYL GROUP HAVING FROM FOUR TO FIVE CARBON ATOMS. 